Renin-angiotensin system and haemostasis gene polymorphisms and outcome after coronary artery bypass graft surgery

BACKGROUND: Coronary artery bypass graft surgery is associated with a considerable 2-year mortality rate. Gene polymorphisms of the renin-angiotensin system may be associated with the risk of hypertension and cardiovascular disease. The angiotensin I-converting enzyme DD genotype has recently been identified as independent predictor of the outcome after coronary artery bypass graft surgery. Genetic factors of the clotting system may be related to the risk of myocardial infarction and restenosis after coronary interventions. The aims of the present study were to investigate whether gene polymorphisms of the renin-angiotensin system (angiotensinogen 235 M/T, angiotensin II type 1 receptor 1166 A/C) or the clotting system (glycoprotein IIIa PlA1/PlA2 and factor V Leiden 1691 G/A) are associated with the outcome after coronary artery bypass grafting. METHODS: A study population of 247 patients was followed-up 2 years after coronary artery bypass graft surgery. The primary end-point was total mortality. The secondary end-point was mortality from cardiac cause or the need for myocardial revascularization (percutaneous coronary interventions or recurrent surgery) during follow-up. Geno typing was performed by polymerase chain reaction- and restriction fragment length polymorphism-based techniques. RESULTS: An older age and the non-use of the internal mammary artery graft were identified as independent predictors of the primary end-point after coronary artery bypass grafting. A decreased left ventricular ejection fraction was an independent predictor for the secondary end-point. No association was found between any of the genetic factors and the outcomes after coronary artery bypass graft surgery in the main factor regression models. However, the angiotensin II type 1 receptor 1166 A/C gene polymorphism modulated the effects of age on the primary end-point, and the angiotensinogen 235 M/T gene polymorphism modulated the effects of age on the secondary end-point. CONCLUSION: We conclude that there are interactions between the angiotensin II type 1 receptor 1166 A/C as well as the angiotensinogen 235 M/T gene polymorphism and age with respect to the outcome after coronary artery bypass graft surgery. The glycoprotein IIIa PlA1/PlA2 and the factor V Leiden 1691 G/A gene polymorphisms were not associated with mid-term mortality or cardiac morbidity after coronary artery bypass grafting.     

One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular-genetic oriented imaging

Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes.     

Polymorphisms of the endothelial nitric oxide synthase gene in women with vulvar cancer

OBJECTIVE: Nitric oxide (NO) is involved in angiogenesis and tumor growth. We attempted to establish an association between two polymorphisms of the endothelial nitric oxide synthase (NOS3) gene and vulvar cancer. METHODS: We used peripheral venous blood sampling, DNA extraction, and polymerase chain reaction (PCR) and pyrosequencing to genotype 68 women with vulvar cancer and 227 healthy Caucasian women for the presence of the intron 4 27-bp-repeat [NOS3*A] and exon 7 Glu298Asp polymorphisms. RESULTS: The presence of a polymorphic NOS3*A allele (26.2% vs. 24.6%; OR: 1.01; 95% CI: 0.6-2.0; P = 0.9) or a polymorphic NOS3 exon 7 Glu298Asp allele (41.2% vs. 53.7%; OR: 0.6; 95% CI: 0.3-1.0; P = 0.09) was not associated with vulvar cancer. Within the vulvar cancer group, the presence of a polymorphic NOS3*A or a polymorphic NOS3 exon 7 Glu298Asp allele was not associated with clinico-pathological parameters such as advanced tumor stage, groin lymph node involvement, tumor grading, and age at diagnosis. Survival analysis demonstrated that the presence of a polymorphic NOS3*A allele was associated with a significantly reduced disease-free survival time (P = 0.03), whereas the presence of the polymorphic NOS3 exon 7 Glu298Asp allele was not associated with disease-free survival (P = 0.5). CONCLUSIONS: We are the first to report on NOS3 polymorphisms in vulvar cancer. We found that allelic variation within intron 4, but not ithin exon 7 of NOS3, influences the length of disease-free survival, but not the biological phenotype of vulvar cancer.     

Neurocognitive deficit following coronary artery bypass grafting: a prospective study of surgical patients and nonsurgical controls

Background

To objectively measure long-term neurocognitive deficit in patients undergoing coronary artery bypass grafting and compare the findings with nonsurgical controls.

Methods

We prospectively measured neurocognitive function in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (n = 104; mean age 64.1 years old; EuroSCORE 2.7 [means]). A cohort of age- and sex-matched patients (n = 80; mean age 63.4 years old) served as nonsurgical controls. After CABG, neurocognitive function was serially reevaluated at 7-day (n = 104), 4-month (n = 100), and 3-year follow-up (n = 88). Neurocognitive function was objectively measured by means of cognitive P300 evoked potentials. Additionally, standard psychometric tests were performed (Trailmaking Test A, Mini Mental State Examination).

Results

As compared to preoperative measures (364 ± 36 ms), cognitive P300 evoked potentials were prolonged (=impaired) at 7-day (381 ± 36 ms; p = 0.001), 4-month (378 ± 31 ms; p = 0.08), and 3-year follow-up (379 ± 35 ms; p = 0.002), respectively. Trailmaking Test A was abnormal, as compared to preoperative, at 3-year follow-up (p < 0.001). Before the operation, surgical patients were fully comparable in P300 measures to nonsurgical controls (363 ± 32 ms; p = 0.362). Most importantly, throughout the entire postoperative follow-up cognitive measures in surgical patients were prolonged (=impaired) as compared with controls (7-day p = 0.001; 4-month p = 0.002 and 3-year p = 0.003, respectively). In stepwise multivariate regression analysis, neurocognitive deficit at 4-month follow-up (p < 0.001), age (p = 0.012), and persistent atrial fibrillation (p = 0.024) were predictive for long-term neurocognitive deficit at 3-year follow-up.

Conclusions

As shown by means of objective measures, and in comparison to nonsurgical controls, coronary artery bypass grafting with cardiopulmonary bypass grafting causes long-term neurocognitive deficit.     

Penile metastasis secondary to follicular thyroid carcinoma

Penile metastases are rare and are considered to reflect end-stage malignant disease. The first case of a follicular thyroid carcinoma metastasizing to the penis is described. Local tumor control and probably enhanced survival was achieved by extended surgery of a previous pelvic recurrence and the penile metastasis and this procedure may be justified in selected cases.     

Mycobacterial peritonitis in pediatric peritoneal dialysis patients

Peritonitis is the most common complication and the leading cause of death in pediatric peritoneal dialysis (PD) patients. According to the most recent data available from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), approximately 25% of pediatric PD patients who die succumb to infection. There are no reported cases of Mycobacterium tuberculosis (MTB) or Mycobacterium avium-intracellulare peritonitis in the NAPRTCS registry. With an increasing incidence of MTB worldwide and the impairment of cellular immunity in chronic renal failure patients, it is not surprising that mycobacterium peritonitis can occur in PD patients. We report two pediatric PD patients with mycobacterial peritoneal infection diagnosed over an 11-year period at our institution. One patient presented with a malfunctioning Tenckhoff catheter and again 3 years later with hyponatremia and ascites. The other presented with recurrent culture-negative peritonitis. These cases illustrate the importance of more extensive evaluation of PD complications, to include evaluation for mycobacterium with special media or peritoneal biopsy, in the above clinical settings if the routine work-up is unrevealing.     

Factors associated with soft drink consumption in school-aged children

OBJECTIVE: To identify factors associated with nonalcoholic carbonated beverage (soft drink) consumption in children. DESIGN: Mail-in surveys collected by Dragonfly, a children's educational magazine distributed nationally to elementary and middle schools, were analyzed. The survey included questions about frequency of soft drink consumption and factors related to soft drink consumption. SUBJECTS AND PARTICIPANTS: The sample consisted of 560 children, 8 to 13 years old, who completed and mailed in the survey. There was an equal distribution of boys and girls (51% and 49%, respectively). STATISTICAL ANALYSES: Frequency distributions were calculated and chi(2) tests were conducted to determine whether soft drink consumption and related factors varied by sex and age. Multivariate logistic regression analyses were conducted to examine the association of soft drink consumption with each factor after adjustment for potential confounders. RESULTS: Preference for the taste of soft drinks was the strongest predictor in the analysis, with those who reported the strongest taste preference 4.50 times more likely (95% confidence interval=2.89-7.04) to consume soft drinks five or more times per week than those with a lower taste preference. Youth whose parents regularly drank soft drinks were 2.88 times more likely (95% confidence interval=1.76-4.72) to consume soft drinks five or more times per week compared with those whose parents did not regularly drink soft drinks. CONCLUSIONS: Results suggest that several factors may be associated with soft drink intake in school-aged children, most notably taste preferences, soft drink consumption habits of parents and friends, soft drink availability in the home and school, and television viewing. Additional research is needed to verify these findings in a representative sample of children.     

Novel nanosensors for rapid analysis of telomerase activity

Elevated telomerase levels are found in many malignancies, offering an attractive target for therapeutic intervention and diagnostic or prognostic purposes. Here we describe the use of a novel nanosensor developed for rapid screens of telomerase activity in biological samples. The technique utilizes magnetic nanoparticles that, on annealing with telomerase synthesized TTAGGG repeats, switch their magnet state, a phenomenon readily detectable by magnetic readers. We tested the efficacy of different telomerase inhibitors in crude human and murine samples and show that phosphorylation of telomerase regulates its activity. High-throughput adaptation of the technique by magnetic resonance imaging allowed processing of hundreds of samples within tens of minutes at ultrahigh sensitivities. Together, these studies establish and validate a novel and powerful tool for rapidly sensing telomerase activity and provide the rationale for developing analogous magnetic nanoparticles for in vivo sensing.